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Spanish flu
From Wikipedia, the free encyclopedia

Public NoticeThe Spanish Flu Pandemic (less misleadingly called the 1918 flu pandemic) was a
pandemic in 1918 and 1919 caused by an unusually severe and deadly strain of the subtype H1N1
of the species Influenza A virus (which apparently killed via cytokine storm, explaining the
severe nature and unusual age distribution). In the 12 months of the pandemic, 50 million to
100 million people worldwide were killed. [1][2]

Despite not having originated in Spain, the Allies of World War I came to call it the "Spanish
Flu". This was mainly because the pandemic received greater press attention in Spain than in
the rest of the world, as Spain was not involved in the war and there was no wartime censorship
in Spain.

Scientists have used tissue samples from frozen victims to reproduce the virus for study.

Contents
1 History
1.1 Patterns of fatality
1.2 Devastated communities
1.3 Unaffected Locales
2 Spanish flu research
2.1 Blood plasma as an effective treatment
3 Sources and notes
4 Further reading
5 External links

[edit] History
The global mortality rate from the 1918/1919 pandemic is not known, but is estimated at 2.5 -
5% of the human population, with 20% of the world population suffering from the disease to some
extent. Influenza may have killed as many as 25 million in its first 25 weeks; in contrast,
AIDS killed 25 million in its first 25 years. Influenza spread across the world, killing more
than 25 million in six months; some estimates put the total killed at over twice that number,
possibly even 100 million.

In the U.S., about 28% of the population suffered, and 500,000 to 675,000 died. In Britain
200,000 died; in France more than 400,000. Entire villages perished in Alaska and southern
Africa. In Australia an estimated 10,000 people died and in the Fiji Islands, 14% of the
population died during only two weeks, and in Western Samoa 22%. An estimated 17 million died
in India, about 5% of India's population at the time. In the Indian Army, almost 22% of troops
who caught the disease died of it.

While World War I did not cause the flu, the close quarters and mass movement of troops
quickened its spread. It has been speculated that the soldiers' immune systems were weakened by
the stresses of combat and chemical attacks, increasing their susceptibility to the disease.

[edit] Patterns of fatality
The strain was unusual for influenza in that this pandemic killed many young adults and
otherwise healthy victims - usual influenzas kill mostly newborns, the old, and the infirm.

People without symptoms could be struck suddenly and within hours be too feeble to walk; many
died the next day. Symptoms included a blue tint to the face and coughing up blood caused by
severe obstruction of the lungs. In later stages, the virus caused an uncontrollable
hemorrhaging that filled the lungs, and patients drowned in their body fluids.

In fast-progressing cases, mortality was primarily from pneumonia, by virus-induced
consolidation. Slower-progressing cases featured secondary bacterial pneumonias, and there may
have been neural involvement that led to psychiatric disorders in a minority of cases. Some
deaths resulted from malnourishment and even animal attacks in overwhelmed communities.

[edit] Devastated communities

Street car conductor in Seattle not allowing passengers aboard without a mask in 1918.While in
most places less than one-third of the population was infected and a fraction of that died, in
a number of towns in several countries the entire population was wiped out.

Even in areas where mortality was low, those incapacitated by the illness were often so
numerous as to bring much of everyday life to a stop. Some communities closed all stores or
required customers not to enter the store but place their orders outside the store for filling.
There were many reports of places with no health care workers to tend the sick because of their
own ill health and no able bodied grave diggers to bury the dead. Mass graves were dug by steam
shovel and bodies buried without coffins in many places.

[edit] Unaffected Locales
In Japan, 257,363 deaths were attributed to influenza by July 1919, giving an estimated 0.425%
mortality rate, much lower than nearly all other Asian countries for which data are available.
The Japanese government severely restricted maritime travel to and from the home islands when
the plague struck. The only sizeable inhabited place with no documented outbreak of the flu in
1918-1919 was the island of Marajó at the mouth of the Amazon River in Brazil. In the Pacific,
American Samoa[3] and the French colony of New Caledonia [4] also succeeded in preventing even
a single death from influenza through effective quarantines.

[edit] Spanish flu research
One theory is that the virus strain originated at Fort Riley, Kansas, by two genetic
mechanisms - genetic drift and antigenic shift - in viruses in poultry and swine which the fort
bred for local consumption. But evidence from a recent reconstruction of the virus suggests
that it jumped directly from birds to humans, without traveling through swine.[5]

In February 1998, a team led by Jeffery Taubenberger of the US Armed Forces Institute of
Pathology (AFIP) recovered samples of the 1918 influenza from the frozen corpse of a Native
Alaskan woman buried for nearly eight decades in permafrost near Brevig Mission, Alaska. Brevig
Mission lost approximately 85% of its population to the Spanish flu in November 1918. One of
the four recovered samples contained viable genetic material of the virus. This sample provided
scientists a first-hand opportunity to study the virus, which was inactivated with guanidinium
thiocyanate before transport. This sample and others found in AFIP archives allowed researchers
to completely analyze the critical gene structures of the 1918 virus. "We have now identified
three cases: the Brevig Mission case and two archival cases that represent the only known
sources of genetic material of the 1918 influenza virus", said Taubenberger, chief of AFIP's
molecular pathology division and principal investigator on the project.

Negative stained transmission electron micrograph (TEM) of recreated 1918 influenza virus.The
February 6, 2004 edition of Science magazine reported that two research teams, one led by Sir
John Skehel, director of the National Institute for Medical Research in London, another by
Professor Ian Wilson of The Scripps Research Institute in San Diego, had managed to synthesize
the hemagglutinin protein responsible for the 1918 outbreak of Spanish Flu. They did this by
piecing together DNA from a lung sample from an Inuit woman buried in the Alaskan tundra and a
number of preserved samples from American soldiers of the First World War. The teams had
analyzed the structure of the gene and discovered how subtle alterations to the shape of a
protein molecule had allowed it to move from birds to humans with such devastating effects.

Wikinews has news related to:
Scientists recreating the 1918 flu virus suggest that it may have come from birdsOn October 5,
2005, researchers announced that the genetic sequence of the 1918 flu strain had been
reconstructed using historic tissue samples. [6]

Influenza viruses have a relatively high mutation rate that is characteristic of RNA viruses.
The H5N1 virus has mutated into a variety of types with differing pathogenic profiles; some
pathogenic to one species but not others, some pathogenic to multiple species. [7] The ability
of various influenza strains to show species-selectivity is largely due to variation in the
hemagglutinin genes. Genetic mutations in the hemagglutinin gene that cause single amino acid
substitutions can significantly alter the ability of viral hemagglutinin proteins to bind to
receptors on the surface of host cells. Such mutations in avian H5N1 viruses can change virus
strains from being inefficient at infecting human cells to being as efficient in causing human
infections as more common human influenza virus types. [8] This doesn't mean one amino acid
substitution can cause a pandemic but it does mean one amino acid substitution can cause an
avian flu virus that is not pathogenic in humans to become pathogenic in humans.

In July 2004, researchers led by H. Deng of the Harbin Veterinary Research Institute, Harbin,
China and Professor Robert Webster of the St Jude Children's Research Hospital, Memphis,
Tennessee, reported results of experiments in which mice had been exposed to 21 isolates of
confirmed H5N1 strains obtained from ducks in China between 1999 and 2002. They found "a clear
temporal pattern of progressively increasing pathogenicity". [9] Results reported by Dr.
Webster in July 2005 reveal further progression toward pathogenicity in mice and longer virus
shedding by ducks.

Recent research of Taubenberger et al has suggested that the 1918 virus, like H5N1, could have
arisen directly from an avian influenza virus. [10] However, researchers at University of
Virginia and Australian National University have suggested that there may be an alternative
interpretation of the data used in the Taubenberger et al. paper.[11][12] Taubenberger et al
responded to these letters and defended their original interpretation. [13]

Other research by Tumpey and colleagues who reconstructed the H1N1 virus of 1918 came to the
conclusion that it is was most notably the polymerase genes and the HA and NA genes that caused
the extreme virulence of this virus. [14] The sequences of the polymerase proteins (PA, PB1,
and PB2) of the 1918 virus and subsequent human viruses differ by only 10 amino acids from the
avian influenza viruses. Viruses with seven of the ten amino acids in the human influenza
locations have already been identified in currently circulating H5N1. This has led some
researchers to suggest that other mutations may surface and make the H5N1 virus capable of
human-to-human transmission. Another important factor is the change of the HA protein to a
binding preference for alpha 2,6 sialic acid (the major form in the human respiratory tract).
In avian virus the HA protein preferentially binds to alpha 2,3 sialic acid, which is the major
form in the avian enteric tract. It has been shown that only a single amino acid change can
result in the change of this binding preference. Altogether, only a handful of mutations may
need to take place in order for H5N1 avian flu to become a pandemic virus like the one of 1918.
However it is important to note that likelihood of mutation does not indicate the likelihood
for the evolution of such a strain; since some of the necessary mutations may be constrained by
stabilizing selection.

[edit] Blood plasma as an effective treatment
When the next pandemic strikes, US Navy researchers suggest a treatment to blunt the effects of
the flu, used during the deadly pandemic of 1918. Some military doctors injected severely
afflicted patients with blood or blood plasma from people who had recovered from the flu. Data
collected during that time indicate that the blood-injection treatment reduced mortality rates
by as much as 50 percent. Navy researchers may launch a test to see if the 1918 treatment will
work against deadly Asian bird flu. Human H5N1 plasma may be an effective, timely, and widely
available treatment for the next flu pandemic. A new international study using modern data
collection methods, would be a difficult, slow process. But many flu experts, citing the
months-long wait for a vaccine for the next pandemic, are of the opinion that the 1918 method
is something to consider.[15]

In the world wide Spanish flu pandemic of 1918, "[p]hysicians tried everything they knew,
everything they had ever heard of, from the ancient art of bleeding patients, to administering
oxygen, to developing new vaccines and sera (chiefly against what we now call Hemophilus
influenzae-a name derived from the fact that it was originally considered the etiological
agent-and several types of pneumococci). Only one therapeutic measure, transfusing blood from
recovered patients to new victims, showed any hint of success."[16]

[edit] Sources and notes
^ NAP
^ Influenza Report
^ Influenza of 1918 (Spanish Flu) and the US Navy
^ World Health Organization Writing Group (2006). "Nonpharmaceutical interventions for pandemic
influenza, international measures.". Centers for Disease Control and Prevention (CDC) Emerging
Infectious Diseases (EID) Journal 12 (1): 189.
^ Sometimes a virus contains both avian adapted genes and human adapted genes. Both the H2N2
and H3N2 pandemic strains contained avian flu virus RNA segments. "While the pandemic human
influenza viruses of 1957 (H2N2) and 1968 (H3N2) clearly arose through reassortment between
human and avian viruses, the influenza virus causing the 'Spanish flu' in 1918 appears to be
entirely derived from an avian source (Belshe 2005)." (from Chapter Two : Avian Influenza by
Timm C. Harder and Ortrud Werner, an excellent free on-line Book called Influenza Report 2006
which is a medical textbook that provides a comprehensive overview of epidemic and pandemic
influenza.)
^ Special report at Nature News: The 1918 flu virus is resurrected, Published online: 5 October
2005; DOI:10.1038/437794a. See: "Characterization of the 1918 influenza virus polymerase genes"
by Jeffery K. Taubenberger, Ann H. Reid, Raina M. Lourens, Ruixue Wang, Guozhong Jin and Thomas
G. Fanning in Nature (2005) volume 437 pages 889-893 DOI:10.1038/nature04230. Also:
"Characterization of the Reconstructed 1918 Spanish Influenza Pandemic Virus" by Terrence M.
Tumpey, Christopher F. Basler, Patricia V. Aguilar, Hui Zeng, Alicia Solórzano, David E.
Swayne, Nancy J. Cox, Jacqueline M. Katz, Jeffery K. Taubenberger, Peter Palese and Adolfo
García-Sastre in Science (2005) volume 310 pages 77-80 DOI:10.1126/science.1119392.
^ New genotype of avian influenza H5N1 viruses isolated from tree sparrows in China by Z. Kou,
F. M. Lei, J. Yu, Z. J. Fan, Z. H. Yin, C. X. Jia, K. J. Xiong, Y. H. Sun, X. W. Zhang, X. M.
Wu, X. B. Gao and T. X. Li in Journal of Virology (2005) volume 79, pages 15460-15466.
^ Evolution of the receptor binding phenotype of influenza A (H5) viruses by A. Gambaryan, A.
Tuzikov, G. Pazynina, N. Bovin, A. Balish and A. Klimov in Virology (2005) electronic release
on October 11 ahead of print publication.
^ The evolution of H5N1 influenza viruses in ducks in southern China by H. Chen, G. Deng, Z.
Li, G. Tian, Y. Li, P. Jiao, L. Zhang, Z. Liu, R. G. Webster and K. Yu in Proceedings of the
National Academy of Sciences of the United States of America (2004) volume 101, pages
10452-10457.
^ Recent research of Taubenberger et al has suggested that the 1918 virus, like H5N1, could
have arisen directly from an avian influenza virus in:
Taubenberger JK, Reid AH, Lourens RM, Wang R, Jin G, Fanning TG. Characterization of the 1918
influenza virus polymerase genes. Nature. October 6, 2005;437(7060):889-893
^ Was the 1918 pandemic caused by a bird flu? - Gibbs and Gibbs Nature. April 27, 2006;440:E8
^ Was the 1918 flu avian in origin? - Antonovics et al. Nature. April 27, 2006;440:E9
^ Molecular virology: Was the 1918 pandemic caused by a bird flu? Was the 1918 flu avian in
origin? (Reply)
^ Tumpey TM, Basler CF, Aguilar PV, Zeng H, Solorzano A, Swayne DE, Cox NJ, Katz JM,
Taubenberger JK, Palese P, Garcia-Sastre A. Characterization of the reconstructed 1918 Spanish
influenza pandemic virus. Science. October 7, 2005;310(5745):77-80
^ npr.org history.navy.mil
^ The Threat of Pandemic Influenza: Are We Ready? Workshop Summary (2005) (free online book)
page 62

Niall Johnson (2006) Britain and the 1918-19 Influenza Pandemic: A Dark Epilogue. Routledge,
London and New York. ISBN 0-415-36560-0
Terrence M. Tumpey, Adolfo García-Sastre, Andrea Mikulasova, Jeffery K. Taubenberger, David E.
Swayne, Peter Palese, and Christopher F. Basler (2002) "Existing antivirals are effective
against influenza viruses with genes from the 1918 pandemic virus". Proceedings of the National
Academy of Sciences 99, 13849-13854.
Alfred W. Crosby (1990). America's Forgotten Pandemic: The Influenza of 1918. Cambridge
University Press. ISBN 0-521-38695-0.
John M. Barry (2004). The Great Influenza: The Epic Story of the Greatest Plague in History.
Viking Penguin. ISBN 0-670-89473-7.
Andrew Noymer and Michel Garenne (2000). "The 1918 Influenza Epidemic's Effects on Sex
Differentials in Mortality in the United States". Population and Development Review,
26(3):565-581.
Geoffrey W. Rice and Edwina Palmer (1993). "Pandemic Influenza in Japan, 1918-19: Mortality
Patterns and Official Responses". Journal of Japanese Studies, 19(2):389-420.
Geoffrey W. Rice, Black November: the 1918 Influenza Pandemic in New Zealand , Canterbury
University Press, 2005 ISBN 1-877257-35-4
Wikimedia Commons has media related to:
Category:Spanish flu
[edit] External links
Nature "Web Focus" on 1918 flu, including new research
Influenza Pandemic on stanford.edu
Article: The Deadliest Fall
Influenza 1918 in the United States on pbs.org
Secrets of the Dead: Killer Flu (PBS)
Flu by Eileen A. Lynch. The devastating effect of the Spanish flu in the city of Philadelphia,
PA, USA
Dialog: An Interview with Dr. Jeffery Taubenberger on Reconstructing the Spanish Flu
The Deadly Virus - The Influenza Epidemic of 1918, by the National Archives and Records
Administration (see actual pictures and records of the time).
The 1918 Influenza Pandemic in New Zealand - includes recorded recollections of people who
lived through it
Experts Unlock Clues to Spread of 1918 Flu Virus - The New York Times
PBS - recovery of flu samples from Alaskan flu victims
An Avian Connection as a Catalyst to the 1918-1919 Influenza Pandemic
Alaska Science Forum - Permafrost Preserves Clues to Deadly 1918 Flu
Pathology of Influenza in France, 1920 Report
"Deadly secret of 1918 flu virus unmasked", Cosmos magazine, September 2006
Yesterday's News blog, 1918 newspaper account on impact of flu on Minneapolis
Retrieved from "http://en.wikipedia.org/wiki/Spanish_flu"
Categories: Aftermath of World War I | Influenza | Pandemics